Act Now or Risk HIV Rebounding

Long-time pharmaceutical company veteran Emilio Emini took over the reins of the HIV program at the Bill & Melinda Gates Foundation over a year ago. Here, he describes the Foundation’s efforts to combat HIV and why this task is more important than ever.

By Kristen Jill Kresge

Bill and Melinda Gates call themselves “impatient optimists.” Backed by a big purse and led by a group of talented and driven individuals, the Bill & Melinda Gates Foundation (BMGF) is striving to make the complex happen. And quickly.

When it comes to HIV, their goal is “to accelerate the decline in HIV infection worldwide and save lives by ensuring expanded and simplified HIV treatment and improved and effective use of interventions to prevent new infections.” It sounds simple, but as with almost everything to do with this virus, it never is.

There is no question that BMGF is a huge player in global health. They are the world’s wealthiest charitable foundation and have already invested billions of dollars in grants focused on improving the health and wellbeing of the world’s poorest. To date, US$3 billion has been invested in HIV alone, with another more than $1.6 billion going to The Global Fund to Fight AIDS, Tuberculosis and Malaria, which supports the expansion of programs offering life-saving antiretroviral (ARV) treatment to the millions of HIV-infected individuals worldwide.

Within BMGF there is a team of influential individuals making their grant decisions and determining how they can work with or through others, whether it be product development partnerships or companies, to drive change. Since last July, the HIV program has been led by Emilio Emini, a seasoned pharmaceutical industry leader with decades of experience in both HIV research generally, and vaccine development in particular. During his career at Merck, Wyeth, and then Pfizer, Emini amassed experience in developing and licensing both drugs and complex vaccines. While at Merck, he led the research team that developed one of the first ARVs against HIV. He also led the company’s vaccine development effort, helping usher HIV vaccine candidates into clinical trials and working on the development and licensure of their vaccines against rotavirus and human papilloma virus. His work in vaccines continued at Wyeth and Pfizer, where he led the effort that resulted in the licensure of the pneumococcal vaccine, Prevnar 13. In between his decades-long experience in the pharmaceutical industry, Emini also served as senior vice president of vaccine development at the International AIDS Vaccine Initiative (IAVI).

In all these roles, Emini brought his vast experience, agile mind, and calm nature to bear on a daunting scientific challenge. In his current position, he remains as determined and practical as ever. When we spoke recently, he emphasized how important it is that efforts to stem the rate of new HIV infections in the hardest-hit places and populations continue to accelerate. “This is not the time to back off,” he says. “I believe we are on the edge of losing control of the epidemic. This is the premise upon which we look at everything that we’re trying to do.” Accelerating a continuing decline in new infections requires sustained funding, improved access to existing treatment and prevention options, and more research into newer and better options to both treat HIV infection and prevent the virus’s spread. And although the goal is ensuring that happens as quickly as possible, Emini understands the heftiness of the task. “The effort that’s going to be required is going to be even harder and more expensive than the efforts we’ve made in the past.”

What is the vision for the HIV program at the Foundation?

Our priorities go across quite a broad range. Our overall priority is to accelerate the decline of the global HIV burden and to continue to accelerate the decline in incidence of new HIV infection.

Obviously, that’s a very broad statement. To do that, we have investments across a large range of activities. Also, and it’s important to note, that while we have the word “global” in our vision statement, our primary focus, albeit not exclusively, is on Southern and Eastern Africa, because that is where we have two-thirds of the burden of HIV infection worldwide. We decided to focus predominantly in those parts of the world because one of our perspectives is that if you’re going to do this well you have to go in depth. Not just in terms of the research and development areas in which we’re focused, but also geographically.

What are the priorities for accomplishing this vision and which of them do you see as the most promising?

Let me describe the challenge first. We know that the global incidence of infection over the last five years has been pretty flat. It’s not continuing to go down substantially as was the case prior to this five-year period. At the same time, in the last 15 years there has been a noted improvement in infant mortality, particularly in Southern Africa. As a result, Africa is right now a very young continent. There is a large population of young people that have grown up and are now entering into that age range—15-24 years of age—in which they are most susceptible to HIV infection.

So if you do the math, given a flat incidence and a substantial increase in the population of young people who are entering into the susceptible age range, the modeling suggests very strongly that 15 years from now we’re going to wind up having, in an absolute sense, a greater number of individuals living with HIV than we currently have, or even had 15 years ago.

It may sound dramatic, but I believe we are on the edge of losing control of the epidemic. And so, when we take a look at where we need to place our investments, we do it in the context of looking towards the next 15 years. If we don’t manage to lower the incidence of HIV infection, especially in high-incidence populations, we will have more people living with HIV, particularly in sub-Saharan Africa, than we have right now. This is the message that Bill Gates delivered at the AIDS 2016 conference back in July when he gave the keynote address. This is the premise upon which we look at everything that we’re trying to do.

Another premise is that you can’t just focus on prevention or treatment. You need to focus on the entire spectrum of what we call the treatment and prevention cascades—you have to look at both ends. When we re-articulated our strategy over the last 12 to 18 months, we divided it into a series of strategic areas that reflect both the treatment end of what needs to be done and the prevention end.

What is the main focus of the treatment work the Foundation invests in?

On the treatment side, we focus first on how to find those people who are living with HIV but who don’t know it, and therefore are not linked to antiretroviral therapy. About 50 percent of individuals who are living with HIV don’t know it, so the first question is how do you find that 50 percent and how do you link them to treatment? We have a number of existing and pending investments in this area.

The next question is, once you have individuals on treatment, and hopefully on fully virally-suppressive treatment, how do you keep them on treatment? There are many sub-questions associated with this area, including how treatment delivery actually is done and the cost of treatment delivery. We focus on improving the efficiency of treatment delivery, the effectiveness of treatment delivery, and the effectiveness of using diagnostic methods such as virus load assessments to determine if treatment is successful.

Our overall focus is on improving end-to-end patient management because the objective is to keep people on fully virus-suppressive treatment for the rest of their lives. We have a broad series of investments in this strategic area.

And what about within prevention?

Our first area of focus in prevention is centered on making the best use of the prevention interventions that we currently have available. There are three efficacious biomedical interventions: voluntary medical male circumcision, so we look at how we could enhance its use; condoms, which are incredibly effective if used consistently, so we look at how to enhance appropriate use and improve condom social marketing; and, most recently, oral pre-exposure prophylaxis, which is just now being introduced in specific at-risk populations in sub-Saharan Africa. Again, the focus here is to do this in the most effective and efficient ways possible.

In addition to these biomedical prevention tools, there are behavioral and structural interventions that are critically important as well. Using all the available prevention tools together to achieve the greatest possible effectiveness and efficiency is the aim of many of our investments.

The next area of prevention focus involves looking towards the future at potentially new biomedical interventions, particularly the development of long-acting anti-HIV prophylactic agents. I am not referring here to vaccines but passively-administered anti-HIV drugs or antibodies that are delivered parenterally to provide a prolonged period of prophylactic protection. There are various manifestations of this approach, including the use of broadly anti-HIV neutralizing monoclonal antibodies and antiretroviral agents that are formulated in ways to give rise to long-acting protection. In essence, we took a page from our family planning colleagues. Contraception becomes very effective when users are provided multiple choices. One can either have the pill once a day, parenteral administration of a contraceptive agent that lasts two to three months, or one can have long-acting implantables. We’ve committed significant investments to help develop the equivalent choices for HIV prevention.

Our final area of HIV prevention focus continues to be centered on the development of a highly effective vaccine. I don’t think I need to say anything more about this other than noting that we continue to very heavily invest in HIV vaccine basic research and basic development efforts. These early development efforts are designed to obtain an understanding of whether a specific vaccine approach that may be potentially effective can, in fact, be successfully developed. While a considerable amount relating to the design of a potentially effective vaccine has been learned over the last 15 years, we still don’t know how close or how far we are to achieving our goal.

Are there developments in the past few years that stand out within the vaccine arena or that you feel particularly optimistic about?

Much of the vaccine-related research work of the past 10 years is clearly encouraging, but until we obtain human clinical data regarding some of the currently more interesting vaccine approaches, I am going to reserve my opinion in terms of optimism. This is an important consideration when it comes to the overall HIV vaccine research and development effort. Human data, by definition, can only be obtained in human clinical studies and, for some of the more promising approaches, these will involve clinical efficacy studies to determine whether promising preclinical observations can be recapitulated in humans. Even with the one clinical study that gave a suggestion of potential efficacy—the RV144 study—the question persists as to whether that specific vaccine approach will yield the same results in high-incidence populations in Southern Africa. We don’t know. We have to do the clinical studies.

This isn’t a trivial issue because human efficacy studies are expensive. We’re talking $100 million to $150 million each. When you look at the list of studies that need to be done eventually in terms of human efficacy, the list may become long. And at $100 million to $150 million per study, this approach represents a significant investment that needs to be made by the HIV vaccine research and development community over the next five to 10 years. Nonetheless, it’s an investment that needs to be made or we won’t know where we stand. We have a lot of preclinical data, a lot of promise, but until we get those human data...

Of course, the human evaluations do not all involve efficacy assessments. There are many clinical studies that need to be done to address earlier questions. For instance, can one come up with a set of immunogens that will elicit broadly neutralizing antibodies? It’s a possibility, but whether or not it can actually be accomplished can only be assessed to a limited extent in preclinical animal models. Until the approaches that have been devised are studied in the context of the human immune system, one cannot provide a reasonable guess as to the likelihood of success.

Given that the research into long-lasting antiretrovirals and passive administration of broadly neutralizing antibodies is already being tested in humans, do you still see a vaccine as being a necessary component of an eventual end to AIDS?

Absolutely. All of the non-vaccine approaches have, at the moment, significant uncertainties associated with them. Even if some of these approaches will be able to demonstrate reasonable efficacy moving forward, that’s just the first step.

The next step is to actually get them used. There remain multiple questions with respect to cost effectiveness and delivery. One of the issues about all preventative interventions is that they have to be used sustainably. The same is also true for vaccines. One has to sustainably maintain the immunization status within a population or protective effectiveness will be lost at both the individual and population level.

Sustainability is an important issue. Underlying all of the strategic focus areas in the foundation’s HIV program is an added strategic focus on sustainability, whether it be for treatment or prevention, for new interventions or the interventions that we currently have. When treatment or prevention interventions are introduced, they have to be introduced in ways which will allow the end-user population to use them sustainably. And the donors who pay for the interventions, including the individual country governments who will have the longer term responsibility for their use, need the information and the data to understand how to maintain the use of these interventions in a sustainable fashion.

Specifically, this entails performing analyses of how incidence of infection is impacted when you introduce a new intervention or when you change how a current intervention is used, and how this information can be used to calculate cost effectiveness to determine whether paying for a given intervention over many years is worthwhile. We don’t ignore the economic aspects of our work. It’s a fundamental part of the work that we’re doing in all of our focus areas. In the absence of doing so, we’re not going to be able to introduce effective interventions in a way that will ensure sustainability over the longer term.

How have you found that the Foundation’s approach has changed or evolved since you took the reins as director of the HIV program?

Well, honestly, a lot of this work was already going on and was going on in very significant ways. I think the only thing that my colleagues and I did since I joined the Foundation was to re-articulate the strategy and place it into defined strategic focus categories. The re-articulation helped because it placed what we’re doing into context. I wouldn’t call it a fundamental sea change—I would say that it is just contextually different.

Given your extensive background in the pharmaceutical industry, is there any more emphasis now on attracting industry or working with them on HIV vaccine research in particular?

We work with different partners and a number of them are industry partners. Some of them are large, some of them are smaller, and we’ve worked with them as needed within our strategic areas. Is the emphasis any more so than it was in the past? No, I think it’s the same.

In addition to industry partners, the foundation works collaboratively with other donors in the HIV area to maintain the research and development focus needed in the field. Some of our biggest partners include: UNAIDS [the Joint United Nations Programme on HIV/AIDS], PEPFAR [the US President’s Emergency Plan for AIDS Relief], USAID [the US Agency for International Development], the NIH [US National Institutes of Health], and the WHO [World Health Organization].

We’re also trying to enhance our engagement with community groups as the importance of community engagement is paramount to our overall effort.

How does the Foundation evaluate its past investments and determine the success of those in spurring progress?

All investments have milestones associated with them, and we evaluate the achievement of the milestones over the life of the investment, and ask where we want the investment to be in terms of its achievements over a defined period of time. In the end, the primary measure that we use is whether the investment has yielded knowledge or an actual intervention that will impact the decline in the incidence of new infection. We then decide whether or not continued investment is worthwhile and appropriate.

In October you were a keynote speaker at the HIV Research for Prevention conference in Chicago. Were there any other key messages you shared with that audience?

One final and critical message is that that this is not the time to step back from our collective global financial commitments related to the control of the HIV epidemic. Even though the successes of the last 15 to 20 years have been pretty remarkable, we’re on the edge of losing control of this epidemic in substantial parts of the world and in some significant populations. The tools that we have are good tools in many cases, but we have to be able to use them better. We also need new tools for the future. The effort that’s going to be required is harder and more expensive than the efforts we put in in the past. We’ve got to keep it up as a global community. This is not the time to back off.

GATES FOUNDATION HIV AREAS OF FOCUS

Improving Diagnosis and Expanding Treatment Coverage BMGF supports the development and appropriate use of novel tools that can greatly increase the number of people who know their status and who seek treatment.

Improving Treatment Retention BMGF supports partners who are working to simplify the delivery of HIV treatment and introduce models of care that are more tailored to the needs of particular populations and their circumstances.

Expanding the Use of Existing Preventive Measures Effective existing measures in preventing HIV infection include voluntary medical male circumcision, condoms, and drugs that reduce the risk of acquiring the virus after exposure. These measures can be effective only if they are affordable and reach high-risk populations—and only if those populations are aware of their risk of contracting HIV.

They also support efforts to improve consistent condom use and the use of drugs that reduce the risk of contracting HIV.

Developing Long-Acting Prevention Measures BMGF supports efforts to develop, evaluate, and introduce innovative approaches to protecting those at risk. These include potential long-acting prevention interventions that can provide continuous protection over a period of time.

Developing an HIV Vaccine BMGF continues to invest in efforts to develop an HIV vaccine. Although developing a highly effective vaccine remains a substantial scientific challenge, even a vaccine with partial efficacy and limited duration could help dramatically reduce the global incidence of HIV.